Mass spectrometry is a common analytical technique used in the physical and biological sciences. Time-of-flight mass spectrometry (TOF-MS) is one mass spectrometry technique used for analytical measurements. TOF-MS has such desirable characteristics as an almost limitless mass range, an ability to provide a complete mass spectrum from each ionization event, and relatively simple operational principles.
A TOF mass spectrometer is composed of an ion injector, a mass analyzer and an ion detector arranged in tandem. A packet of ions derived from a sample is input to the ion injector. The packet of ions is typically composed of ions of multiple, different ion species having respective mass-to-charge ratios. An electrical pulse applied to the ion injector imparts approximately the same initial kinetic energy to all the ions in the packet of ions in such a manner that the ions all move in the same direction of travel. The ions of each ion species travel at a respective velocity that depends on the mass-to-charge ratio of the ion species. The ions pass into the mass analyzer, which, in its simplest implementation, is an elongate evacuated chamber. In the mass analyzer, the differing velocities of the different ion species cause the ions of the respective ion species to separate in the direction of travel. At the distal end of the mass analyzer, the ions are incident on the ion detector, which measures the abundance of ions incident thereon within successive narrow time-of-flight windows to produce a time-of-flight spectrum. The time-of-flight spectrum represents the relationship between ion abundance and time of flight. Since the time of flight of the ions of a given ion species is proportional to the square root of the mass-to-charge ratio of the ion species, the time-of-flight spectrum can be converted directly to a mass spectrum that represents the relationship between ion abundance and mass-to-charge ratio. In this disclosure, for brevity, term mass-to-charge ratio will be abbreviated as mass.
The mass resolution in a mass spectrometer is defined as T/2ΔT, where T is the measured time of flight at a given mass, and ΔT is the measured or calculated time-of-flight spread. For a TOF mass spectrometer, the square root dependence of the time of flight on the mass dictates that, for large masses, the peak separation decreases inversely with the square root of the ion mass. In recent years there has been a significant increase in applications of mass spectrometry to large biological molecules. Such applications have mass resolution demands that exceed the capabilities of conventional TOF-MS systems. To make TOF mass spectrometers, with their many other desirable characteristics, viable for use in such applications, their mass resolution must be increased.
The mass resolution of a TOF mass spectrometer is proportional to the length of the flight path between the ion injector and the detector. A typical TOF mass spectrometer has a linear flight path. Increasing the physical length of such linear flight path until the required resolution is reached would increase the physical dimensions of the instrument beyond those considered reasonable. One solution is to use a multiply-reflected folded flight path, in which the flight path between ion injector and ion detector has a zigzag trajectory in which the ions are reflected at multiple apexes in the flight path by respective gridless electrostatic mirrors. A zigzag flight path provides a significant increase in the flight path length within the overall dimensions of a conventional instrument. The ion mirrors perform spatial focusing to reduce ion losses and keep the beam confined regardless of the number of reflections. However, aligning the multiple electrostatic mirrors during fabrication can be difficult. Moreover, even though the zigzag arrangement decreases the maximum dimensions of the evacuated space in which the ions travel, it may undesirably increase the overall volume of the evacuated space.
Using only two electrostatic mirrors in a coaxial arrangement reduces the severity of the post-fabrication alignment problem but undesirably reduces the mass range that can be measured. Other zigzag configurations suffer from a lack of ion focusing in the plane of the zigzag ion path. This undesirably allows the ion beam to diverge after only a few reflections, which reduces the maximum practical length of the flight path. Using intermediate periodic ion lenses reduces beam spreading but adds complexity to the mass spectrometer.
Accordingly, what is needed is a mass analyzer for a time-of-flight mass spectrometer that provides a substantially increased ion flight path length without a commensurate increase in the volume of the evacuated space and that is easy to fabricate.